This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Despite the well known association of stress, anxiety and depression, the impact of anxiety and stressful life events on the neurobiological observations reported in depression have not been clearly. examined. Stress and anxiety may set in motion a series of neurobiological events including activation of the body's major stress-defense systems and activation of brain circuitry involved in the acquisition and maintenance of fear. In this study, MRI techniques, including morphometric MRI, MRS, and fMRI, will be used to examine the role of stress and anxiety in modulating structural, chemical and functional measures of depression. Based on neuroanatomical measures of depression we will focus on two main brain areas, both known to be vulnerable to stress: the hippocampus and the prefrontal cortex. Depressed subjects will be thoroughly characterized on measures of comorbid anxiety and history of early and recent trauma/stress. Ten depressed subjects and then matched healthy controls, recruited at the Mount Sinai Medical Center, will undergo morphometric MRI, MRS and fMRI testing. A major strength of this protocol lies in the analysis of cross-modal data, allowing the exploration of questions about the relationship between neurochemistry and function, and the influence of anxiety on neurobiological findings in depression, in an integrative manner